title: Protective effects of veskamide, enferamide, becatamide, and oretamide on H2O2-induced apoptosis of PC-12 cells.
abstract: Veskamide, enferamide, becatamide, and oretamide are phenolic amides whose analogues are found in plants. In this study, the four amides were prepared by chemical synthesis and their protective effects on H(2)O(2)-induced apoptosis in PC-12 cells were investigated. The syntheses were relatively simple and the yields were more than 43%. Using NMR spectroscopic methods, the chemical structures of veskamide, enferamide, becatamide, and oretamide were confirmed. The decreasing order of the protective effects on H(2)O(2)-induced apoptosis was becatamide>enferamide≥oretamide>veskamide. In fact, becatamide suppressed H(2)O(2)-induced mitochondrial membrane depolarization in a dose-dependent manner. At the concentration of 10 μM, becatamide maintained mitochondrial membrane depolarization at 16% compared to 51% in H(2)O(2)-treated PC-12 cells (P<0.05). Also, at the same concentration, becatamide inhibited H(2)O(2)-induced caspase-9 activation and caspase-independent chromatin condensation by 68% (P<0.05) and 73% (P<0.05), respectively. This is the first report about the chemical synthesis of becatamide and its potential biological activity to inhibit H(2)O(2)-induced apoptosis of PC-12 cells via protecting mitochondrial membrane integrity, thereby suppressing caspase-9 activation and chromatin condensation.
authors.affiliation: Diet, Genomics, and Immunology Laboratory, Bldg. 307C, Rm. 131, BHNRC, ARS, USDA, Beltsville, MD 20705, USA. jae.park@ars.usda.gov
authors.forename: Jae B
authors.initials: JB
authors.lastname: Park
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001549:Benzamides / Q000138:chemical synthesis / Q000494:pharmacology*; D019817:Benzoic Acid / Q000737:chemistry; D053453:Caspase 9 / Q000378:metabolism; D002843:Chromatin / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D053078:Membrane Potential, Mitochondrial; D015394:Molecular Structure; D016716:PC12 Cells; D020011:Protective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D014439:Tyramine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D014641:Vanillic Acid / Q000737:chemistry
chemical_list: D000577:Amides; D001549:Benzamides; D002843:Chromatin; D062385:Hydroxybenzoates; D020011:Protective Agents; C561781:becatamide; C561779:enferamide; C561780:oretamide; C561778:veskamide; C009091:protocatechuic acid; D005707:Gallic Acid; D019817:Benzoic Acid; D006861:Hydrogen Peroxide; C001945:syringic acid; D053453:Caspase 9; D014641:Vanillic Acid; D014439:Tyramine